The sensorimotor transformations underlying many types of behavior are inherently stochastic, meaning that sensory input modulates the probability of a response, but fails to trigger it. Contrary to intuition, a stochastic sensorimotor transformation is the optimal response in certain frequently encountered behavioral situations. For example, economic game theory has demonstrated that in pairwise competition for scarce resources, a person's optimal strategy is to behave in a manner that is irreducibly uncertian from his/her opponent's point of view, and this theory has been shown to apply to animal behavior as well. Other situations where stochastic sensorimotor transformations are favored include visual-saccadic decision making, preditor escape responses and spatial orientation in unpredictable environments. Despite the widespread adaptive significance of stochastic sensorimotor transformations, little is known about their neuronal basis. Where does the randomness reside and what is its biophysical basis? We propose to address these questions using chemotaxis behavior in the nematode C. elegans as the experimental system. C. elegans chemotaxis involves a biased random walk, making this behavior a paradigmatic example of a response regulated by a stochastic sensorimotor transformation. Moreover, this organism offers many unusual experimental advantages including a compact nervous system of only 302 neurons, a nearly complete anatomical wiring diagram, and a wide range of electrophysiological and optophysiological techniques for linking the activity of identified neurons to behavior. The proposed research investigates the stochastic sensorimotor transformations using a novel approach to activate presynaptic sensory neurons and interneurons while recording from postsynaptic neurons that presumably transform this stimulus into a stochastic response. The mechanisms that are responsible for stochastic sensorimotor transformation have significant implications for neurological health, as sensorimotor deficits are the primary manifestation of many neurological diseases. More than 60% of all human disease genes have a correlate in C. elegans. Furthermore, C. elegans has been used successfully in the past to uncover the molecular actions of wellknown neuro-active drugs. Experience has shown that cellular level mechanisms in invertebrates frequently have counterparts in vertebrates;thus the synaptic and biophysical physiology of sensorimotor transformations in C. elegans may well reveal fundamental mechanisms responsible for sensorimotor control in humans.